As established by various studies, it is recognized that cholesterol and triglycerides play a major role in the formation of artherosclerotic plaques by accelerating the deposition of blood lipids in the arterial wall.
The compound 4-(2-naphthalenylmethyl)amino)benzoic acid has been reported in the literature by Rydon et al. at J. Chem. Soc. 1962, pages 4689-4695. The ethyl ester of 4-(((1,3-benzodioxol-5-yl)methyl)amino)benzoic acid is described in German Pat. No. 716,668 (CA38:2346). The free acid is not described and is novel. Neither of the known compounds was reported as useful in lowering serum lipid levels in animals.
Reports in the literature include p-benzylaminobenzoic acid itself. CA51:8720g; 52:18498d; 52:P8539c 55:5867c; 57:14973c. Reported monosubstituted p-benzylaminobenzoic acids include various amino, nitro, and methoxy substitutions. CA65:7001f and CA64:20105g. Several simple multi-substituted analogs have also been reported. CA52:16630b and CA75:141136j. No hypolipidemic activity has been mentioned for any of these compounds. Related compounds are disclosed in U.S. Pat. Nos. 3,257,191; 3,674,843; 3,674,844; 3,780,027 and 3,268,394.
Very few hypolipidemic benzoic acids have been reported until recently. The most important hypolipidemic derivative of benzoic acid disclosed to date is tibric acid. U.S. Pat. No. 3,843,662 and U.S. Pat. No. 3,855,255; see Ryan et al. Clinc. Pharmacol. Therap., 15,218 (1974). There have been two reports of hypolipidemic activity in p-amino benzoic acid analogs. Ger. Offen. No. 2,316,914 (CA82:43070h) and Derwent Abstract BE815-703. A number of patents have issued describing hydroxy and thio benzoic acid derivatives as hypolipidemics or for use in the treatment of heart disease. Japanese Pat. No. 7,333,742 (CA80:133072y); Japanese Pat. No. 7,333,743 (CA80:133073z); German Offen. No. 2,311,020 (CA82:16563g); U.S. Pat. No. 3,716,644; U.S. Pat. No. 3,732,295; Japanese Pat. No. 7,368,541 (CA80:59739c); Derwent Abstract J4 9,070,942; German Offen. No. 1,963,187 (CA75:63401a); Derwent Abstract 805,172; Arznei Forsch., 22 (2) 465-8 (1972); U.S. Pat. No. 3,856,951; and Derwent Abstract 2,149,070. Alkylamino benzoic acid derivatives have also been described as hypolipidemic agents. U.S. Pat. No. 3,868,416. In addition, there has been much work with compounds having unsaturated bonds for their liquid crystal properties. Derwent Abstract J4 9,052,785 and British Pat. No. 1,373,609.